Chromium propionate in broilers: effect on insulin sensitivity.

The objective of this study was to evaluate the effects of dietary chromium (Cr), as chromium propionate, on measures of insulin sensitivity. Liver and muscle glycogen, and plasma glucose and non-esterified fatty acid (NEFA) concentrations were used as indicators of insulin sensitivity. In total, 288 newly hatched male Ross broilers were divided into 4 dietary treatments consisting of 0 (control diet analyzed 0.43 to 0.45 mg Cr/kg), 0.2, 0.4, or 0.6 mg supplemental Cr/kg diet, resulting in 4 treatments with 9 replicate pens per treatment containing eight birds per pen. At d 21, 2 birds per cage were removed based on the greatest deviation from pen mean BW, resulting in each pen containing 6 birds for the final analyses. Final BW were taken on d 40, and on d 42 two birds from each pen were sampled for plasma NEFA, glucose, and muscle and liver glycogen determination at the initiation and termination of a 22 h fast. The remaining 2 fasted birds were sampled after a 30 min refeeding period. No differences were observed in feed intake, BW gain, or feed efficiency on d 21 or d 40. Liver glycogen tended (P=0.10) to be greater in Cr-supplemented chicks in the fed state, and muscle glycogen concentrations tended (P=0.07) to be greater in Cr-supplemented chicks compared with controls following fasting and refeeding. Plasma glucose concentrations were not affected by dietary Cr in the fed, fasted, or refed state. Plasma NEFA levels were not affected by treatment in fed or fasted birds. However, plasma NEFA concentrations were lower (P<0.01) in chicks supplemented with Cr than in controls following fasting and refeeding, suggesting that Cr increased insulin sensitivity. No differences were detected among birds supplemented with 0.2 or 0.4 mg Cr/kg, and among those receiving 0.4 or 0.6 mg Cr/kg. Results of this study indicate that Cr propionate supplementation of a control diet containing 0.43 to 0.45 mg Cr/kg enhanced insulin sensitivity.

Determinants of potassium channel assembly localised within the cytoplasmic C-terminal domain of Kv2.1.

The C-terminal domain of the voltage-gated potassium channel Kv2.1 is shown to have a role in channel assembly using dominant negative experiments in Xenopus oocytes. Kv2.1 channel polypeptides were co-expressed with a number of polypeptide fragments of the cytosolic C-terminus and the assembly of functional channel homotetramers quantified electrophysiologically using the two electrode voltage clamp technique. Co-expression of C-terminal polypeptides corresponding to the final 440, 318, 220 and 150 amino acid residues of Kv2.1 all resulted in a significant reduction in the functional expression of the full-length channel. A truncated version of Kv2.1 lacking the final 318 amino acids of the C-terminal domain (Kv2. 11-535) exhibited similar electrophysiological properties to the full-length channel. Co-expression with either the 440 or 318 residue polypeptides resulted in a reduction in the activity of the truncated channel. In contrast, the 220 and 150 residue C-terminal fragments had no effect on Kv2.11-535 activity. These data demonstrate that C-terminal interactions are important for driving Kv2.1 channel assembly and that distinct regions of the C-terminal domain may have differential effects on the formation of functional tetramers.

Determination of the analgesic 3-phenoxy-N-methylmorphinan in plasma by gas chromatography using either positive chemical ionization mass spectrometric or nitrogen-phosphorus-specific detection analysis.

The compound 3-phenoxy-N-methylmorphinan (I) is under development as an analgesic agent. Studies on the biotransformation of the drug in the rat and in the dog have shown that I is extensively metabolized by N-demethylation to yield the nor-analogue (I-A), by para-hydroxylation of the 3-phenoxy ring to yield the phenolic analogue (I-B), cleavage of the ether linkage to yield levorphanol (I-C), and its N-demethylation to yield nor-levorphanol (I-D). The presence of these four metabolites (two of which, I-B and I-C, have analgesic potential) in addition to the parent drug, necessitated the development of sensitive and specific assays for their quantitation in plasma. This was accomplished by the development of (a) a high-performance liquid chromatographic assay using UV detection to obtain a qualitative/semi-quantitative profile of the metabolites present in plasma; (b) a gas chromatographic--nitrogen--phosphorus-specific detection method for the determination of the parent drug (I) for pre-clinical drug evaluation; and (c) a sensitive and specific gas chromatographic--positive chemical ionization mass spectrometric assay for eventual clinical evaluation for the determination of I and a key metabolite levorphanol (I-C). This report presents some preliminary pharmacokinetic data on I and I-C in the dog obtained during pre-clinical development.